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High risk multiple myeloma: Definition, treatment, and more

Multiple myeloma is a type of cancer affecting the bone marrow plasma cells. A subgroup of people with this condition may have high risk multiple myeloma. Treating high risk multiple myeloma can be challenging, but some options are available.

While treatments for people with multiple myeloma have advanced significantly in the past 10 years, people with high risk multiple myeloma still have poor outcomes.

Research into novel therapy options would be beneficial for providing better care to people with high risk multiple myeloma. Some options might include using a novel combination of drugs to elicit complete responses to the condition. A complete response indicates that treatment has led to the disappearance of all signs of the cancer.

Keep reading to learn more about high risk multiple myeloma, including its definition, how it compares to standard risk, and current research on the topic.

A 2021 article describes people with high risk multiple myeloma as a subgroup of people with multiple myeloma who experience poorer disease outcomes than expected.

Additionally, research suggests that multiple myeloma affects people differently, especially their response to treatment and chances of survival. Due to these factors and advances in the diagnosis and therapeutics, many definitions exist for people with high risk multiple myeloma.

Doctors may find it challenging to diagnose and treat people with high risk multiple myeloma.

People with multiple myeloma survive for around 10 years on average. However, the outlook is not so favorable for people with high risk multiple myeloma.

Between 10–20% of people with multiple myeloma die within 2–3 years following diagnosis. People in this subgroup can be classified as having high risk multiple myeloma.

Standard risk multiple myeloma may be treatable. Treatment options might include:

  • Systemic treatments for their condition, such as drug therapy or stem cell transplantation.
  • Supportive treatments, such as drugs, to treat low blood cell counts.
  • A combination of treatments.

However, for some people, standard treatments do not work. These are people with high risk multiple myeloma. Experts have linked this more aggressive form of the disease to certain genetic changes. High risk multiple myeloma is also less responsive to treatment and more likely to result in a relapse sooner.

The presence of the following characteristics shows that a person’s multiple myeloma is in the high risk subgroup:

  • frailty
  • extramedullary disease — a condition where myeloma cells form tumors in the organs or soft tissues
  • plasma cell leukemia — a rare type of cancer in which a person’s blood contains unusually high levels of abnormal plasma cells
  • high risk cytogenetic abnormalities — irregularities in how the body’s cells and chromosomes interact
  • relapsing sooner than expected
  • R ISS-3 (Revised International Staging System, stage III) — when the protein serum β2 microglobulin (Sβ2M) reaches levels greater than 5.5 milligrams per liter (mg/l) in the blood

The treatment approach to high risk multiple myeloma may involve:

  • induction therapy: This is the first phase of treatment given to a person with myeloma.
  • Autologous stem cell transplants, if appropriate: This involves replacing damaged stem cells with healthy ones.
  • Maintenance therapy: Medications that doctors prescribe after cancer has disappeared initially.

Doctors may recommend certain regimens of therapy, according to the person’s transplant eligibility.

2016 research reports on treatments showing positive results in high risk cytogenetic diseases, such as those present in people with high risk multiple myeloma. These include the use of proteasome inhibitors — drugs that prevent the breakdown of proteins — along with:

Doctors may also prescribe corticosteroids, such as dexamethasone.

Previously, doctors may have tailored treatment based on a person’s age. However, more recently, they base treatment on how frail the person is, or whether they also have other diseases.

Research indicates that doctors should aim to provide the best evidence treatment — triplet therapy — whenever possible. Triplet therapy refers to the administration of an immunomodulatory drug, a proteasome inhibitor drug, and a steroid.

Doctors may slightly alter the regimen in some cases. For example, if a person is frail, the doctor might choose to prescribe lower doses of lenalidomide and dexamethasone.

Clinical trials have been looking into finding new treatments for people with high risk multiple myeloma:

OPTIMUM/MUK nine trial

During the OPTIMUM/MUK nine clinical trial, 107 people with “ultra-high risk” multiple myeloma. University of Leeds, Myeloma UK, Celgene, and Janssen, are collaborators on this trial.

Researchers identified people with ultra-high risk multiple myeloma using cytogenetic and gene profiling tests. Cytogenetic tests can assess changes in a person’s chromosomes, whereas gene expression profiling measures gene activity in the body’s cells. Cytogenetic tests may also involve taking tissue, blood, or bone marrow samples.

This trial aims to provide an intensive treatment regimen. People with ultra-high risk multiple myeloma received high dose chemotherapy, a stem cell transplant, and a combination of the following five drugs:

Trial participants then received further rounds of consolidation treatment, which kills any remaining cancer cells let in the body, and maintenance treatment.

The researchers of this study estimate the study to be completed in June 2023.

CAR T cell therapy

This is a type of immunotherapy that targets specific antigens that are heavily present in cancer cells. An attractive target is an antigen called B cell maturation antigen (BCMA).

CAR T cells can produce fast and deep responses in people with relapsed refractory multiple myeloma. Newer trials are looking into implementing this therapy type for the high risk subgroup.

Learn more about CAR T cell therapy here.

High risk multiple myeloma refers to a subgroup of people with multiple myeloma that may not respond well to standard therapies and have poorer outcomes.

While there are several treatment options for multiple myeloma, this is not the case for the high risk subgroup. Research looking into new methods of treatment for this population is currently underway.

One clinical trial is currently examining a new way to treat people with high risk multiple myeloma. This involves cytogenetic tests and gene expression profiling to better understand the biology of the disease.

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